US3624088A - Trichloro-ethylidine amino quinolines - Google Patents

Trichloro-ethylidine amino quinolines Download PDF

Info

Publication number
US3624088A
US3624088A US815238A US3624088DA US3624088A US 3624088 A US3624088 A US 3624088A US 815238 A US815238 A US 815238A US 3624088D A US3624088D A US 3624088DA US 3624088 A US3624088 A US 3624088A
Authority
US
United States
Prior art keywords
amino
ethylidine
trichloro
mol
trichloroethylidene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US815238A
Inventor
Pal Benko
Zoltan Budai
Laszlo Pallos
Edit Berenyi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Egyesult Gyogyszer es Tapszergyar
Egyt Gyogyszervegyeszeti Gyar
Original Assignee
Egyt Gyogyszervegyeszeti Gyar
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar
Application granted granted Critical
Publication of US3624088A publication Critical patent/US3624088A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/58—Nitro radicals

Definitions

  • the invention relates to the preparation of new 5,3,3- trichloroethylidene amine derivatives having anthelmintic and fungicide activity.
  • This reaction may be carried out in the presence or absence of a solvent, e.g. of benzene, toluene or xylene it is in some cases preferable to distill off the water fonned during the reactron.
  • a solvent e.g. of benzene, toluene or xylene it is in some cases preferable to distill off the water fonned during the reactron.
  • the new compounds of the formula I are solid crystalline products decomposing easily under the influence of heat; some of them have low melting points or are even liquid at room temperature. Because of their heat sensitivity they can be purified only by recrystallization. in order to avoid the contamination of the product by unreacted trichloroacetaldehyde, it is preferable carry out the above reaction with a slight excess of the amine of the formula 11.
  • the compounds of the formula 1 obtained as described above may be converted into acid addition salts by the usual methods.
  • the anthelmintic acting of the new compounds of the general formula 1 has been tested against the parasites Enchytraeus albidus (E), Tubifex rivulorum (T) and Schistasma mansoni cercaria (S); the inhibiting concentrations are given in the following table; the corresponding values obtained with the following known anthelmintic agents are shown for comparison:
  • METHYRIDIN i.e. Z-(B-methoxyethyl)-pyridine (B) and MIRAClL-D, i.e. l-diethylaminoethylamino-4-methylthiaxanthone (C)
  • METHYRIDIN i.e. Z-(B-methoxyethyl)-pyridine (B) and MIRAClL-D, i.e. l-diethylaminoethylamino-4-methylthiaxanthone
  • C Minimal inhibiting concentration mgJIiter (A)
  • EXA PLE l A mixture of 13.5 g. (0.096 mol.) of S-amino quinoline and 13.22 g. (0.09 mol.) of trichloroacetaldehyde in 150 ml. of benzene is refluxed for 3 hours and the solvent is then distilled ofi in vacuo.
  • the 8-(B,fl,B-trichloroethylidene)-amino-quinoline is a crystalline product melting at 58-62 C.
  • EXAMPLE 5 17.86 g. (0.1 mol.) of 4-amino-7-chloro-quinoline are dissolved in 500 m1. of toluene and 14.74 g. (0.1 mol.) trichloroacetaldehyde are added thereto. After ceasing of the exotherrn reaction the mixture is refluxed for 6 hours and then the product is collected by filtration. 23.6 g. of 4-(fi,B,/3- trichloroethylidene) -amino-7-chloro-quinoline (76.6 percent of the theoretical yield) are obtained; m.p. l68-169 C.
  • EXAMPLE 6 22.05 g. (0.15 mol.) of l-amino-S ,6,7,8- tetrahydronaphthalene and 22.1 1 g. (0.15 mol.) of trichloroacetaldehyde in 250 ml. of xylene are reacted at C. for 3 hours. The reaction mixture is then evaporated in vacuo and the residue is distilled under 3 mm. mercury at 161-162 C. 21.6 g. of 1-(flfifi-trichloroethylidineamino5,6,7,8-tetrahydronaphthalene (52.2 percent of the theoretical yield) are obtained.
  • a compound of the formula AN CHCCI wherein A represents a quinolyl-4 or quinolyl-S group unsubstituted or substituted by halogen, lower alkyl or nitro, and the phannaceutically acceptable acid addition salts thereof.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Trichloro ethylidine amine derivatives of quinolines, thiazoles and tetrahydronaphthalenes having anthelmonthic and fungicidal activity are disclosed.

Description

llnited States Patent Inventors Pal Benko;
Zoltan Budai; Laszlo Pallos;
Edit Berenyi, nee Poldermann, all of Budapest, Hungary Apr. 10, 1969 Nov. 30, 1971 Egyesult Gyogyszer-es Tapszergyar Apr. 12, 1968 Hungary TRICHLORO-ETHYLIDINE AMINO QUINOLINES 3 Claims, No Drawings US. Cl
260/288, 7l/90, 71/94, 7 l/l2l, 424/258, 424/270. 424/330, 260/286, 260/297R, 260/306.8, 260/328,
[51] Int. Cl C07d 33/52 [50] Field of Search...
Hamilton...
Poos
Primary Examiner- Donald G. Daus AlrurneyMcGlew and Toren ABSTRACT: Trichloro ethylidine amine derivatives of quin olines. lhiazoles and tetrahydronaphthalenes having anthelmonthic and fungicidal activity are disclosed.
The invention relates to the preparation of new 5,3,3- trichloroethylidene amine derivatives having anthelmintic and fungicide activity.
it has been found that the new fl,/3,B-trichloroethylidene amine derivatives of the general formula I wherein A represents a quinolyl group unsubstituted or substituted by halogen, lower alkyl or nitro groups, a Z-thiazolyl group unsubstituted or substituted by one or two methyl groups or a tetrahydronaphthyl group, have valuable anthelmintic and fungicide properties and can be used also as intermediate products for the preparation of further valuable compounds, e.g. of forrnamidine derivatives having anthelmintic and herbicide activity.
These new Bfifi-trichloroethylidene derivatives can be prepared by a method known per se but used hitherto only for the preparation of analogous compounds containing alkyl or phenyl groups attached to the nitrogen atom (of. Chem. Ber. 100, l8l4/l967l); this method comprises reacting trichloroacetaldehyde with a quinolyl, 2-thiazolyl or tetrahydronaphthyl amine of the general formula 11 A-NH (11) wherein A has the same meaning as above.
This reaction may be carried out in the presence or absence of a solvent, e.g. of benzene, toluene or xylene it is in some cases preferable to distill off the water fonned during the reactron.
The new compounds of the formula I are solid crystalline products decomposing easily under the influence of heat; some of them have low melting points or are even liquid at room temperature. Because of their heat sensitivity they can be purified only by recrystallization. in order to avoid the contamination of the product by unreacted trichloroacetaldehyde, it is preferable carry out the above reaction with a slight excess of the amine of the formula 11.
The compounds of the formula 1 obtained as described above may be converted into acid addition salts by the usual methods.
The anthelmintic acting of the new compounds of the general formula 1 has been tested against the parasites Enchytraeus albidus (E), Tubifex rivulorum (T) and Schistasma mansoni cercaria (S); the inhibiting concentrations are given in the following table; the corresponding values obtained with the following known anthelmintic agents are shown for comparison:
YOMESAN, i.e. N-(2'-chloro-4'-nitrophenyl)-5-chloro-salicylic amide (A),
METHYRIDIN, i.e. Z-(B-methoxyethyl)-pyridine (B) and MIRAClL-D, i.e. l-diethylaminoethylamino-4-methylthiaxanthone (C) Minimal inhibiting concentration mgJIiter (A) |5.5 15.5 31 (B) 15.5-31 7.5-l5.5 15.5 (C) 3.5-7.5 3.5-7.5 7.5
The preparation of the new compounds is shown in more details by the following exam les.
EXA PLE l A mixture of 13.5 g. (0.096 mol.) of S-amino quinoline and 13.22 g. (0.09 mol.) of trichloroacetaldehyde in 150 ml. of benzene is refluxed for 3 hours and the solvent is then distilled ofi in vacuo. The 8-(B,fl,B-trichloroethylidene)-amino-quinoline is a crystalline product melting at 58-62 C.
EXAMPLE 2 A mixture of 15.5 g. (0.1 mol.) of 2-amino-5-nitrothiazol and 14.8 g. (0.1 mol.) of trichloroacetaldehyde in ml. of benzene is refluxed for 3 hours, the reaction mixture is then cooled and the precipitated 2-([i.Bfi-trichloroethylidene)- amino-S-nitrothiazol is collected; m.p. 187-188 C.
EXAMPLE 3 twenty grams (0.2 mol.) of 2-aminothiazol are reacted with 29.48 g. (0.2 mol.) of trichloroacetaldehyde in 500 ml. of abs. benzene at 80 C.; the water formed is distilled off and separated during the reaction. After 3 hours the reaction product is collected by filtration. 42.3 g. of 2 (8,5,5- trichloroethylidene)-amino-thiazol (92 percent of the theoretical yield) are obtained; m.p. 146l47 C.
EXAMPLE 4 22.6 g. (0.19 mol.) of 2-amino-4-methyl-thiazol and 27.9 g. (0.19 mol.) of trichloroacetaldehyde in 250 ml. of benzene are refluxed for 3 hours. During this time the initially 2-phase mixture becomes homogeneous and a precipitate appears at the end of the reaction. After cooling, the precipitate is collected by filtration; 43.5 g. of 2-(B,B,B-trichloroethylidene)-amino- 4-methyl-thiazol (89,3 percent of the theoretical yield) are obtained, m.p. 165-l 66 C. (decomp.
EXAMPLE 5 17.86 g. (0.1 mol.) of 4-amino-7-chloro-quinoline are dissolved in 500 m1. of toluene and 14.74 g. (0.1 mol.) trichloroacetaldehyde are added thereto. After ceasing of the exotherrn reaction the mixture is refluxed for 6 hours and then the product is collected by filtration. 23.6 g. of 4-(fi,B,/3- trichloroethylidene) -amino-7-chloro-quinoline (76.6 percent of the theoretical yield) are obtained; m.p. l68-169 C.
EXAMPLE 6 22.05 g. (0.15 mol.) of l-amino-S ,6,7,8- tetrahydronaphthalene and 22.1 1 g. (0.15 mol.) of trichloroacetaldehyde in 250 ml. of xylene are reacted at C. for 3 hours. The reaction mixture is then evaporated in vacuo and the residue is distilled under 3 mm. mercury at 161-162 C. 21.6 g. of 1-(flfifi-trichloroethylidineamino5,6,7,8-tetrahydronaphthalene (52.2 percent of the theoretical yield) are obtained.
We claim:
1. A compound of the formula AN=CHCCI wherein A represents a quinolyl-4 or quinolyl-S group unsubstituted or substituted by halogen, lower alkyl or nitro, and the phannaceutically acceptable acid addition salts thereof.
2. 8-([3,3,B-trichloroethylidene)-aminoquinoline.
3. 4-(B,B,B-trichloroethylidene )-amino-7-chloroquinoline.

Claims (2)

  1. 2. 8-( Beta , Beta , Beta -trichloroethylidene)-aminoquinoline.
  2. 3. 4-( Beta , Beta , Beta -trichloroethylidene)-amino-7-chloroquinoline.
US815238A 1968-04-12 1969-04-10 Trichloro-ethylidine amino quinolines Expired - Lifetime US3624088A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HUEE001505 1968-04-12

Publications (1)

Publication Number Publication Date
US3624088A true US3624088A (en) 1971-11-30

Family

ID=10995250

Family Applications (2)

Application Number Title Priority Date Filing Date
US815238A Expired - Lifetime US3624088A (en) 1968-04-12 1969-04-10 Trichloro-ethylidine amino quinolines
US00154178A Expired - Lifetime US3751423A (en) 1968-04-12 1971-06-17 Trichloroethylidene-amino-thiazoles

Family Applications After (1)

Application Number Title Priority Date Filing Date
US00154178A Expired - Lifetime US3751423A (en) 1968-04-12 1971-06-17 Trichloroethylidene-amino-thiazoles

Country Status (6)

Country Link
US (2) US3624088A (en)
BE (1) BE731424A (en)
FI (1) FI48835C (en)
GB (1) GB1238416A (en)
IL (1) IL31989A (en)
SE (1) SE358156B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3696106A (en) * 1968-01-23 1972-10-03 Boehringer Sohn Ingelheim N,n{40 -bis-{8 (1-amido 2,2,2 trichloro)-ethyl{9 -piperazine
US3874874A (en) * 1970-11-05 1975-04-01 Air Prod & Chem Herbicidal method employing thiadiazolyl amidines

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2653940A (en) * 1951-01-27 1953-09-29 William S Johnson Process for preparing 4-quinolyl secondary amines
US3000894A (en) * 1957-10-31 1961-09-19 Diamond Alkali Co Chloral derivatives of amino quinoline
US3002001A (en) * 1958-04-03 1961-09-26 Sterling Drug Inc 4-alkylimino-1-[aromatic-(lower - alkyl)]-1,4-dihydroquinolines and their preparation
US3374233A (en) * 1964-08-03 1968-03-19 Searle & Co N-amino-17alpha-aza-d-homoandrost-5-en-3beta-ol and hydrazones thereof
US3501487A (en) * 1967-06-29 1970-03-17 Mcneilab Inc Certain hetero-aryl lower alkylene derivatives of 1 - lower alkyl - 2-imino-pyrrolidines

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2653940A (en) * 1951-01-27 1953-09-29 William S Johnson Process for preparing 4-quinolyl secondary amines
US3000894A (en) * 1957-10-31 1961-09-19 Diamond Alkali Co Chloral derivatives of amino quinoline
US3002001A (en) * 1958-04-03 1961-09-26 Sterling Drug Inc 4-alkylimino-1-[aromatic-(lower - alkyl)]-1,4-dihydroquinolines and their preparation
US3374233A (en) * 1964-08-03 1968-03-19 Searle & Co N-amino-17alpha-aza-d-homoandrost-5-en-3beta-ol and hydrazones thereof
US3501487A (en) * 1967-06-29 1970-03-17 Mcneilab Inc Certain hetero-aryl lower alkylene derivatives of 1 - lower alkyl - 2-imino-pyrrolidines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3696106A (en) * 1968-01-23 1972-10-03 Boehringer Sohn Ingelheim N,n{40 -bis-{8 (1-amido 2,2,2 trichloro)-ethyl{9 -piperazine
US3874874A (en) * 1970-11-05 1975-04-01 Air Prod & Chem Herbicidal method employing thiadiazolyl amidines

Also Published As

Publication number Publication date
SE358156B (en) 1973-07-23
FI48835B (en) 1974-09-30
GB1238416A (en) 1971-07-07
IL31989A0 (en) 1969-06-25
US3751423A (en) 1973-08-07
DE1918042B2 (en) 1975-08-28
BE731424A (en) 1969-09-15
FI48835C (en) 1975-01-10
DE1918042A1 (en) 1969-12-11
IL31989A (en) 1973-01-30

Similar Documents

Publication Publication Date Title
AU2010201457B2 (en) 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridine-2-yl-amino]-propionic acid ethyl ester methane sulphonate and use thereof as a medicament
JPH0555506B2 (en)
KR850001226B1 (en) Process for preparing imidazolylpyridine therapeutic agents
US5017581A (en) Pyridonecarboxylic acids and their anti-bacterial compositions
US4119721A (en) Substituted (3-loweralkylamino-2-r1 o-propoxy)pyridines, their preparation and use
US4404214A (en) 2-Pyridinecarboxamide derivatives compositions containing same and method of using same
US3624088A (en) Trichloro-ethylidine amino quinolines
US3752823A (en) N alkyl tetrahydrocarbazoles
US2606906A (en) 1-(2-pyridyl) piperazine and process of preparing same
US3772301A (en) (4-substituted)4-(methylsulfinyl)methylcarbostyrils
NZ280258A (en) Quinoxaline derivatives; preparative method and medicaments
US5155223A (en) Preparation of quinolinecarboxylic acids
US4192880A (en) 2-Substituted benzimidazole compounds
US4297357A (en) N-Phenethylacetamide compounds and process for preparation thereof
CA1154015A (en) Tetrahydroquinoline derivatives, a process for their preparation, their use, and pharmaceutical formulations containing them
US2829084A (en) Certain alkyl-n
CA1038379A (en) Acylated 2-aminothiazole derivatives and a process for the preparation thereof
US4665173A (en) 2-acetyl- and 2-propionylpyridine selenosemicarbazones
IL45995A (en) 4-pyridylthiazole-2-carboxamides and acetamides their preparation and pharmaceutical compositions containing them
US4436740A (en) 3-Cycloalkylamino-2-OR-propoxycyanopyridines
US3215697A (en) Novel 4-oxo-1, 2, 3, 4-tetrahydroquinazolines
US3177219A (en) Ylethyi
US2954381A (en) Heteroaryloxazolidinediones
US4742068A (en) Dihydropyridine compounds having 1,4,4-trisubstitution useful as antihypertensive agents
US2187847A (en) Condensation products of butyrolactones and primary amines of the aromatic and heterocyclic series